Core A: While pluripotent stem cells and their differentiated progeny have tremendous promise for cardiac repair, their routine culture is demanding and requires considerable expertise and continuous attention to quality control. Based on our extensive prior experience with these cells, we have found that centralization of cell culture efforts is the best way to ensure consistency and efficiency in the large-scale production of undifferentiated and differentiated cells. Hence, the primary goal ofthe Stem Cell Core will be to generate large numbers of undifferentiated embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and cardiac derivatives for distribution to the individual projects in this program. The Core will also work closely with investigators in Project 2 to optimize the derivation of cardiomyocytes from canine ESCs. Finally, the Core will also develop and share optimized protocols for the genetic modification of ESCs and iPSCs, including the generation of cell type specific reporter lines via transgenesis in bacterial artficial chromosomes (BACs). In sum, the Core will undertake three specific aims: 1) to provide the individual projects with the stem cells and cardiac derivatives needed to complete their respective aims, 2) to develop BAC transgenesis and optimize the delivery of modified BACs into human ESCs and iPSCs), and 3) to provide training and technical assistance with in vitro experiments involving pluripotent stem cells or their differentiated progeny.